Investigational Gene Therapy for Cystinosis Obtains FDA’s Orphan Drug Designation

By Ruchi Jhonsa, Ph.D.

It is an everyday fight for people suffering from cystinosis. Affecting one in a hundred thousand people, Cystinosis is a rare but debilitating lysosomal storage disorder disease caused by the accumulation of amino acid cystine in lysosomes. If left untreated, Cystinosis can damage kidneys to a point where it can no longer function. In fact, 90 percent of the people affected require kidney transplant before the age of 20. The current method of treatment for the disorder is one pill of cysteamine, a cystine-clearing drug, every six hours. Although the treatment is effective, it is also burdensome, as the patient needs a frequent and daily dose of the drug with dozen of other drugs and supplements round the clock.

In the need of the hour, scientists are using new-age technologies to treat the disease. At AVROBIO, a leading clinical-stage company, scientists are working towards developing a gene therapy called AVR-RD-04 to treat cystinosis by modifying the patient’s hematopoietic stem and progenitor cells (HSPC).  Autologous stem cell transplant or HSPC transplantation has been tested as a treatment option for several lysosomal storage disorders based on the idea that HSPC can travel to, proliferate and populate the affected tissue compartments. Using this property of the stem cell, HSPC can be modified as desired and injected back in the patient where they will populate the organs affected with modified cells.

AVROBIO today announced that its investigational gene therapy, AVR-RD-04 has been granted orphan drug designation by the U.S. FDA. With this designation, the company will get seven years of FDA administered market exclusivity, tax credits of up to 50% of R&D costs, R&D grants and may receive tax benefits in clinical trials. It is good news for AVROBIO, as the orphan designation will provide support to the company financially during drug testing.

The Phase 1/2 Clinical Trial

AVR-RD-04 is an investigational gene therapy for cystinosis that works by extracting the patient’s hematopoietic stem cells and modifying them outside the body to produce a functional cystinosin protein. In the open-label, single-arm Phase 1/2 clinical trial these cells will be injected back into the patient and its efficacy and safety will be evaluated. Currently, the study is being conducted by the company’s academic collaborators at UCSD and is led by Stephanie Cherqui, PhD associate professor of pediatrics at UCSD’s School of Medicine and a consultant to the company. The trial is actively enrolling up to six participants and is funded by grants to UCSD from California Institute for Regenerative Medicine as well as Cystinosis Research Foundation (CRF).

 

Lots of Hope for the Drug

It looks like this drug can work after all. The clinical trials are underway for the treatment of a lysosomal storage disorder known as metachromatic leukodystrophy using the HSPC strategy. It was observed that all the nine patients in the trial had successful HSPC transplantation and HSPC were able to populate and express arylsulfatase A, a protein deficient in this LSD disorder. Another trial for X-lined cerebral adrenoleukodystrophy (ALD) also showed positive signs as 17 boys treated with the HSPC therapy showed expression of ALD protein otherwise missing in their cells.

CEO and President at AVROBIO, Geoff MacKay expressed his belief in the drug and said, “People living with cystinosis need new treatment options to keep cystine from accumulating in the lysosomes of cells, which leads to corneal damage and kidney deterioration, among other complications. Although the current standard of care has improved the outlook for this community, it does not halt disease progression or a wide range of debilitating complications, which can severely impact daily lives. We believe lentiviral gene therapy is potentially well suited to comprehensively address these symptoms, since it is designed to restore functional cystinosin throughout the body and brain”.

Related Article: FDA Issues Guidances Supporting Development of Gene Therapy Products

References
  1. https://investors.avrobio.com/news-releases/news-release-details/avrobio-receives-orphan-drug-designation-us-fda-avr-rd-04

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